Many important hormone and growth factor responses are mediated through the action of macromolecular receptors with high binding affinity for the respective hormone ligand. The glucocorticoid receptor is a cytoplasmic receptor that migrates to the nucleus and induces a number of alterations in gene activity after binding a member of the glucocorticoid family. Most receptors are present at low concentrations in responsive tissues, and are difficult to purify in quantity. The characterization of various receptors, both in terms of gene organization, and in terms of protein structure and function, would benefit enormously from the availability of molecular clones for the receptor loci. Attempts are underway to isolate and characterize clones for the glucocorticoid receptor from human cells. Two approaches have been taken; one involves the preparation of cDNA expression libraries from receptor competent cells, followed by clone identification with antisera to the receptor; the other involves identification of the receptor genomic locus by insertional mutation with retrovirus vectors.